Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000–2021: a systematic analysis from the Global Burden of Disease Study 2021
Authors: Azalea M Thomson, Theresa A McHugh, Assaf P Oron, Corey Teply, Nikhil Lonberg, Victor Vilchis Tella, Lauren B Wilner, Kia Fuller, Hailey Hagins, Richard Gyan Aboagye, Melka Biratu Aboye, Eman Abu-Gharbieh, Ahmed Abu-Zaid, Isaac Yeboah Addo, Bright Opoku Ahinkorah, Aqeel Ahmad, Saif Aldeen S AlRyalat, Hubert Amu, Aleksandr Y Aravkin, Judie Arulappan, Maha Moh'd Wahbi Atout, Ashish D Badiye, Sara Bagherieh, Maciej Banach, Morteza Banakar, Mainak Bardhan, Amadou Barrow, Deriba Abera Bedane, Isabela M Bensenor, Akshaya Srikanth Bhagavathula, Pankaj Bhardwaj, Prarthna V Bhardwaj, Ajay Nagesh Bhat, Zulfiqar A Bhutta, Mariah Malak Bilalaga, Jessica Devin Bishai, Saeid Bitaraf, Archith Boloor, Muhammad Hammad Butt, Vijay Kumar Chattu, Dinh-Toi Chu, Omid Dadras, Xiaochen Dai, Bardia Danaei, Anh Kim Dang, Fitsum Wolde Demisse, Meghnath Dhimal, Daniel Diaz, Shirin Djalalinia, Deepa Dongarwar, Muhammed Elhadi, Mohamed A Elmonem, Christopher Imokhuede Esezobor, Farshid Etaee, Oghenowede Eyawo, Adeniyi Francis Fagbamigbe, Ali Fatehizadeh, Lisa M Force, William M Gardner, Kazem Ghaffari, Paramjit Singh Gill, Mahaveer Golechha, Pouya Goleij, Vivek Kumar Gupta, Hamidreza Hasani, Treska S Hassan, Mohammed Bheser Hassen, Segun Emmanuel Ibitoye, Adalia I Ikiroma, Chidozie C D Iwu, Peter Bai James, Shubha Jayaram, Rime Jebai, Ravi Prakash Jha, Nitin Joseph, Farnaz Kalantar, Himal Kandel, Ibraheem M Karaye, Woldeteklehaymanot Dagne Kassahun, Imteyaz A Khan, Shaghayegh Khanmohammadi, Adnan Kisa, Farzad Kompani, Kewal Krishan, Iván Landires, Stephen S Lim, Preetam Bhalchandra Mahajan, Soleiman Mahjoub, Azeem Majeed, Bishnu P Marasini, Haftu Asmerom Meresa, Tomislav Mestrovic, Sonica Minhas, Awoke Misganaw, Ali H Mokdad, Lorenzo Monasta, Ghulam Mustafa, Tapas Sadasivan Nair, Sreenivas Narasimha Swamy, Hasan Nassereldine, Zuhair S Natto, Muhammad Naveed, Biswa Prakash Nayak, Jean Jacques Noubiap, Taylor Noyes, Chisom Adaobi Nri-ezedi, Vincent Ebuka Nwatah, Chimezie Igwegbe Nzoputam, Ogochukwu Janet Nzoputam, Osaretin Christabel Okonji, Adeyinka Omoniyi Onikan, Mayowa O Owolabi, Jay Patel, Siddhartha Pati, Shrikant Pawar, Ionela-Roxana Petcu, Frédéric B Piel, Ibrahim Qattea, Mehran Rahimi, Mosiur Rahman, Salman Rawaf, Elrashdy Moustafa Mohamed Redwan, Nazila Rezaei, Basema Saddik, Umar Saeed, Fatemeh Saheb Sharif-Askari, Abdallah M Samy, Austin E Schumacher, Elaheh Shaker, Adithi Shetty, Migbar Mekonnen Sibhat, Jasvinder A Singh, Muhammad Suleman, Dev Ram Sunuwar, Mindy D Szeto, Jacques JL Lukenze Tamuzi, Nathan Y Tat, Birhan Tsegaw Taye, Mohamad-Hani Temsah, Muhammad Umair, Sahel Valadan Tahbaz, Cong Wang, Nuwan Darshana Wickramasinghe, Arzu Yigit, Vahit Yiğit, Ismaeel Yunusa, Burhan Abdullah Zaman, Moein Zangiabadian, Peng Zheng, Simon I Hay, Mohsen Naghavi, Christopher J L Murray, Nicholas J Kassebaum
Journal: The Lancet Haematology (2023)

Previous global analyses, with known underdiagnosis and single cause per death attribution systems, provide only a small insight into the suspected high population health effect of sickle cell disease. Completed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, this study delivers a comprehensive global assessment of prevalence of sickle cell disease and mortality burden by age and sex for 204 countries and territories from 2000 to 2021.We estimated cause-specific sickle cell disease mortality using standardised GBD approaches, in which each death is assigned to a single underlying cause, to estimate mortality rates from the International Classification of Diseases (ICD)-coded vital registration, surveillance, and verbal autopsy data. In parallel, our goal was to estimate a more accurate account of sickle cell disease health burden using four types of epidemiological data on sickle cell disease: birth incidence, age-specific prevalence, with-condition mortality (total deaths), and excess mortality (excess deaths). Systematic reviews, supplemented with ICD-coded hospital discharge and insurance claims data, informed this modelling approach. We employed DisMod-MR 2.1 to triangulate between these measures-borrowing strength from predictive covariates and across age, time, and geography-and generated internally consistent estimates of incidence, prevalence, and mortality for three distinct genotypes of sickle cell disease: homozygous sickle cell disease and severe sickle cell β-thalassaemia, sickle-haemoglobin C disease, and mild sickle cell β-thalassaemia. Summing the three models yielded final estimates of incidence at birth, prevalence by age and sex, and total sickle cell disease mortality, the latter of which was compared directly against cause-specific mortality estimates to evaluate differences in mortality burden assessment and implications for the Sustainable Development Goals (SDGs).Between 2000 and 2021, national incidence rates of sickle cell disease were relatively stable, but total births of babies with sickle cell disease increased globally by 13·7% (95% uncertainty interval 11·1-16·5), to 515 000 (425 000-614 000), primarily due to population growth in the Caribbean and western and central sub-Saharan Africa. The number of people living with sickle cell disease globally increased by 41·4% (38·3-44·9), from 5·46 million (4·62-6·45) in 2000 to 7·74 million (6·51-9·2) in 2021. We estimated 34 400 (25 000-45 200) cause-specific all-age deaths globally in 2021, but total sickle cell disease mortality burden was nearly 11-times higher at 376 000 (303 000-467 000). In children younger than 5 years, there were 81 100 (58 800-108 000) deaths, ranking total sickle cell disease mortality as 12th (compared to 40th for cause-specific sickle cell disease mortality) across all causes estimated by the GBD in 2021.Our findings show a strikingly high contribution of sickle cell disease to all-cause mortality that is not apparent when each death is assigned to only a single cause. Sickle cell disease mortality burden is highest in children, especially in countries with the greatest under-5 mortality rates. Without comprehensive strategies to address morbidity and mortality associated with sickle cell disease, attainment of SDG 3.1, 3.2, and 3.4 is uncertain. Widespread data gaps and correspondingly high uncertainty in the estimates highlight the urgent need for routine and sustained surveillance efforts, further research to assess the contribution of conditions associated with sickle cell disease, and widespread deployment of evidence-based prevention and treatment for those with sickle cell disease.Bill & Melinda Gates Foundation.